Specific Aim 1: Develop a method for recording the focal EOG in response to a centrally presented light stimulus. Over the first two years of this protocol we completed a series of experiments to establish the stimulus parameters that produce a focal EOG in healthy volunteers. Briefly, a 40 cd/m2 stimulus is necessary generate a light rise from a stimulus area of 40 centered on the macula. This is smaller than the mean Arden ratio of 2.4 observed with full-field stimulation. Our derived method for recording focal EOG requires that the background light be turned off for 10 seconds every minute, which is a departure from normal EOG testing. To determine whether these two methods produce different results, full-field EOGs were recorded from two healthy volunteers under identical conditions except for the two background conditions. The light rise portion of the intermittent background was within 10% of the continuously on-background indicating no meaningful difference between the background presentations. The results above indicate that our method can measure an EOG light rise using a centrally presented 40 deg stimulus. Specific Aim 2: Testing in healthy volunteers to determine intra- and inter-session variability. As noted for Aim 1, we have established the optimal stimulus parameters that produce a focal EOG in healthy volunteers. In 14 healthy volunteers, the Light peak:baseline ratio averaged 1.370.19. We have not yet attempted to measure variability in the focal EOG response. Specific Aim 3: Examine the focal EOG in participants with macular disease. To validate our method for recording focal EOG responses, we recorded the focal EOG from a targeted group of seven Stargardt patients with macular atrophy but foveal preservation. These patients had good visual acuity that meant they could follow the oscillating fixation targets which are used during EOG testing. In several participants, the focal EOG was absent and full-field EOG present as predicted. However, in the remaining Stargardt patients, there was a focal EOG of variable amplitude. We speculate that the size of atrophy was not a sufficiently large portion of the focal EOG stimulus size (40 deg) in some participants to reduce the light rise response. Our initial results with Stargardt patients whilst promising were not sufficient to confirm that the focal EOG was truly a local response. As a result, we have switched out focus to recording the focal EOG from coloboma patients. In this case, we are targeting patients with large uveal colobomas (>= 40 deg) that have good visual acuity; i.e. the coloboma does not involve the optic disc or fovea. We reasoned that such patients would have no light rise when our stimulus is projected over the coloboma. This would be an important proof of principle since it would confirm that scattered light from our stimulus is not sufficient to drive a light rise from the remaining healthy retina. The other prediction is that such patients would have a normal full-field EOG and normal rod responses with the Medmont (protocol 16-EI-0024) in areas outside the coloboma. We have recorded from two patients with large uveal colobomas. No focal EOG was recordable in either participant as predicted. Patients with colobomas that meet our specifications are rare but we are hopeful of recruiting and recording several more of these patients to confirm our focal EOG method. For our final proof of principle experiment we need patients with large colobomas (>= 40 deg) with relatively good visual acuity (20/50 or better) and who are mature enough to complete the lengthy testing required. We have not been able to recruit new coloboma patients over the last year. However, we have recently identified two patients that meet our criteria. One is due to return to the NEI clinic in May 2019 and we hope to recruit the other patient later this year.